Our laboratory has pioneered studies on the existence of mammosomatotropes - cells that release both growth hormone (GH) and prolactin (PRL) - in pituitaries of normal rats. Previously, our efforts have been aimed at characterizing these dual secretors along with their monohormonal counterparts. Now, we will shift our focus to the development of cells that release these hormones. The long-term objective of the proposed research is to answer four very fundamental questions about the development and lineage of cells that secrete GH and PRL, either separately or simultaneously. The questions are: 1) What is the precise ontogenic pattern of cells that secrete GH, PRL, or both hormones in rats and how is this regulated? 2) What are the functional characteristics of the initial GH and/or PRL cells and how do they change during development? 3) To what extent do GH cells give rise to PRL cells during development? and, 4) Is the mammosomatotrope a transitional cell for the functional interconversion of GH and PRL cells in the adult as it appears to be in the neonate? We plan to take a multifaceted approach to these problems. Reverse hemolytic plaque assays will be employed to analyze hormone secretion at the single cell level. Recombinant DNA strategies will provide complementary information on gene expression. Finally, hormonal deficits will be created surgically at the whole animal level to identify putative regulatory factors. Thus, by integrating information derived from studies at multiple levels of organizational complexity - cellular, molecular and organismal - we intend not only to establish the developmental patterns, functional diversity and ontogenic lineage of GH and PRL secretors, but also to gain insight into the physiologic importance of single and dual hormone secretors. It is anticipated that the proposed studies will provide valuable information toward our basic understanding of GH and PRL regulatory processes. Such knowledge is essential for identifying the causes of, and developing treatments for, GH and/or PRL secreting adenomas of the pituitary. Moreover, the rat provides an excellent model for understanding the differentiation of GH and/or PRL secreting cells in humans since these species are remarkably similar in terms of ontogenic patterns of cells which release these hormones.